Women of childbearing age are at high risk for major depressive disorder (MDD). The lifetime risk for MDD in community samples has varied from 10-25 percent for women, with peak prevalence between 25-44 years of age. Despite these facts, information to guide women and physicians through a consideration of antidepressant use during pregnancy is limited. The American Psychiatric Association Committee on Research on Psychiatric Treatments identified MDD during pregnancy as a priority area for generation of treatment recommendations. In addition to separation of the effects of exposure to drug from exposure to MDD less than the work group identified areas in which data are urgently needed: 1) whether minor physical anomalies occur with greater frequency in drug-exposed infants, 2) if maternal weight gain and infant birth weight are compromised by drug exposure, 3) replication of the sole study which addresses behavioral teratogenicity, and 4) management strategies to reduce neonatal toxicity. Obtaining this information is the impetus for this grant application. The antidepressants to be investigated are the serotonin specific reuptake inhibitors (SSRI), because these agents have become first-line treatments for MDD. The study is a 5-year prospective, naturalistic investigation of the effects of treatment of pregnant women with SSRI. Three groups of mothers will be recruited over the first three years of the study and they and their children will be followed for 24 months post-birth. The pregnant women: 1) treated with an SSRI who are nondepressed, 2) with MDD who do not take SSRI, and 3) without MDD or SSRI treatment. Data from this investigation will increase our sophistication in making risk-benefit decisions during pregnancy.